CN105050612B - 用于药物递送的组合物和方法 - Google Patents

用于药物递送的组合物和方法 Download PDF

Info

Publication number: CN105050612B
Authority: CN; China
Prior art keywords: peptide; seq; ldlr; interest; peptides
Prior art date: 2012-10-19
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

CN201380065295.4A

Other languages

English (en)

Chinese (zh)

Other versions

CN105050612A (zh

Inventor

G.雅克夸特

P.勒科切

Jd.马尔科

N.佩罗特

M.戴维

Y.莫利诺

M.克雷斯特查蒂斯基

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Aix Marseille Universite

Centre National de la Recherche Scientifique CNRS

Vect Horus

Original Assignee

Centre National de la Recherche Scientifique CNRS

Universite de la Mediterranee Aix Marseille II

Vect Horus

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2012-10-19

Filing date

2013-10-18

Publication date

2018-04-20

2012-10-19 Priority claimed from US13/655,954 external-priority patent/US8877716B2/en

2013-10-18 Application filed by Centre National de la Recherche Scientifique CNRS, Universite de la Mediterranee Aix Marseille II, Vect Horus filed Critical Centre National de la Recherche Scientifique CNRS

2015-11-11 Publication of CN105050612A publication Critical patent/CN105050612A/zh

2018-04-20 Application granted granted Critical

2018-04-20 Publication of CN105050612B publication Critical patent/CN105050612B/zh

Status Active legal-status Critical Current

2033-10-18 Anticipated expiration legal-status Critical

Links

238000000034 method Methods 0.000 title claims abstract description 40
239000000203 mixture Substances 0.000 title claims abstract description 27
239000003814 drug Substances 0.000 title abstract description 40
108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 279
210000004027 cell Anatomy 0.000 claims abstract description 97
239000003068 molecular probe Substances 0.000 claims abstract description 13
102000004196 processed proteins & peptides Human genes 0.000 claims description 88
239000013543 active substance Substances 0.000 claims description 44
239000000126 substance Substances 0.000 claims description 39
230000001225 therapeutic effect Effects 0.000 claims description 37
239000003795 chemical substances by application Substances 0.000 claims description 33
230000008878 coupling Effects 0.000 claims description 30
238000010168 coupling process Methods 0.000 claims description 30
238000005859 coupling reaction Methods 0.000 claims description 29
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 28
150000001413 amino acids Chemical group 0.000 claims description 27
150000001875 compounds Chemical class 0.000 claims description 24
-1 hydroxymethylene, hydroxyethylene, dihydroxyethylene, hydroxyethylamine Chemical class 0.000 claims description 24
235000001014 amino acid Nutrition 0.000 claims description 21
125000006850 spacer group Chemical group 0.000 claims description 16
238000002059 diagnostic imaging Methods 0.000 claims description 15
125000000524 functional group Chemical group 0.000 claims description 15
108090000623 proteins and genes Proteins 0.000 claims description 14
239000012216 imaging agent Substances 0.000 claims description 13
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 12
235000018102 proteins Nutrition 0.000 claims description 12
102000004169 proteins and genes Human genes 0.000 claims description 12
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims description 12
210000004899 c-terminal region Anatomy 0.000 claims description 11
235000018417 cysteine Nutrition 0.000 claims description 10
239000004471 Glycine Substances 0.000 claims description 9
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 8
150000007523 nucleic acids Chemical class 0.000 claims description 8
230000008569 process Effects 0.000 claims description 8
239000000546 pharmaceutical excipient Substances 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 7
LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 claims description 6
108010077895 Sarcosine Proteins 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 6
229960001639 penicillamine Drugs 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 5
230000002209 hydrophobic effect Effects 0.000 claims description 5
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 claims description 5
108020004707 nucleic acids Proteins 0.000 claims description 5
102000039446 nucleic acids Human genes 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 claims description 4
HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 claims description 4
108010039918 Polylysine Proteins 0.000 claims description 4
238000003776 cleavage reaction Methods 0.000 claims description 4
238000010353 genetic engineering Methods 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229920000656 polylysine Polymers 0.000 claims description 4
229940043230 sarcosine Drugs 0.000 claims description 4
230000007017 scission Effects 0.000 claims description 4
230000021615 conjugation Effects 0.000 claims description 3
239000000816 peptidomimetic Substances 0.000 claims description 3
229920001184 polypeptide Polymers 0.000 claims description 3
150000003335 secondary amines Chemical class 0.000 claims description 3
DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 claims description 3
MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical group NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 claims description 3
108010002156 Depsipeptides Proteins 0.000 claims description 2
230000010933 acylation Effects 0.000 claims description 2
238000005917 acylation reaction Methods 0.000 claims description 2
230000009435 amidation Effects 0.000 claims description 2
238000007112 amidation reaction Methods 0.000 claims description 2
238000004132 cross linking Methods 0.000 claims description 2
230000032050 esterification Effects 0.000 claims description 2
238000005886 esterification reaction Methods 0.000 claims description 2
ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 claims description 2
ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 claims description 2
125000005541 phosphonamide group Chemical group 0.000 claims description 2
PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 2
OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 claims description 2
239000000710 homodimer Substances 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 1
230000008499 blood brain barrier function Effects 0.000 abstract description 79
210000001218 blood-brain barrier Anatomy 0.000 abstract description 79
102000005962 receptors Human genes 0.000 abstract description 36
108020003175 receptors Proteins 0.000 abstract description 36
206010028980 Neoplasm Diseases 0.000 abstract description 30
230000004888 barrier function Effects 0.000 abstract description 28
230000004378 blood-retinal barrier Effects 0.000 abstract description 27
238000003384 imaging method Methods 0.000 abstract description 25
201000011510 cancer Diseases 0.000 abstract description 24
210000000170 cell membrane Anatomy 0.000 abstract description 20
210000000056 organ Anatomy 0.000 abstract description 18
239000000539 dimer Substances 0.000 abstract description 17
210000004100 adrenal gland Anatomy 0.000 abstract description 15
238000003745 diagnosis Methods 0.000 abstract description 14
210000000936 intestine Anatomy 0.000 abstract description 14
210000004185 liver Anatomy 0.000 abstract description 14
239000008280 blood Substances 0.000 abstract description 12
230000001404 mediated effect Effects 0.000 abstract description 12
210000004369 blood Anatomy 0.000 abstract description 11
241000124008 Mammalia Species 0.000 abstract description 6
210000000653 nervous system Anatomy 0.000 abstract description 6
229940002612 prodrug Drugs 0.000 abstract description 6
239000000651 prodrug Substances 0.000 abstract description 6
230000036541 health Effects 0.000 abstract description 4
229920000642 polymer Polymers 0.000 abstract description 4
230000007170 pathology Effects 0.000 abstract description 2
210000000278 spinal cord Anatomy 0.000 abstract description 2
241001597008 Nomeidae Species 0.000 abstract 2
101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 description 96
102100024640 Low-density lipoprotein receptor Human genes 0.000 description 70
210000004556 brain Anatomy 0.000 description 52
210000001519 tissue Anatomy 0.000 description 50
239000000562 conjugate Substances 0.000 description 39
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 37
230000027455 binding Effects 0.000 description 35
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
229940079593 drug Drugs 0.000 description 30
238000000338 in vitro Methods 0.000 description 29
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
210000003169 central nervous system Anatomy 0.000 description 27
230000032258 transport Effects 0.000 description 26
238000011282 treatment Methods 0.000 description 26
210000004155 blood-retinal barrier Anatomy 0.000 description 25
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 23
108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 23
238000002474 experimental method Methods 0.000 description 23
210000002889 endothelial cell Anatomy 0.000 description 22
201000010099 disease Diseases 0.000 description 21
241000699670 Mus sp. Species 0.000 description 20
230000012202 endocytosis Effects 0.000 description 20
241000282414 Homo sapiens Species 0.000 description 18
108010007622 LDL Lipoproteins Proteins 0.000 description 18
241000700159 Rattus Species 0.000 description 18
238000003786 synthesis reaction Methods 0.000 description 18
102000007330 LDL Lipoproteins Human genes 0.000 description 17
230000015572 biosynthetic process Effects 0.000 description 17
208000035475 disorder Diseases 0.000 description 16
239000003446 ligand Substances 0.000 description 15
230000008685 targeting Effects 0.000 description 15
208000015114 central nervous system disease Diseases 0.000 description 13
239000011347 resin Substances 0.000 description 13
229920005989 resin Polymers 0.000 description 13
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
238000011068 loading method Methods 0.000 description 12
239000000243 solution Substances 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
238000009826 distribution Methods 0.000 description 11
125000005647 linker group Chemical group 0.000 description 11
230000010412 perfusion Effects 0.000 description 11
230000014509 gene expression Effects 0.000 description 10
238000002347 injection Methods 0.000 description 10
239000007924 injection Substances 0.000 description 10
102100025566 Chymotrypsin-like protease CTRL-1 Human genes 0.000 description 9
101000856199 Homo sapiens Chymotrypsin-like protease CTRL-1 Proteins 0.000 description 9
238000002866 fluorescence resonance energy transfer Methods 0.000 description 9
229960002449 glycine Drugs 0.000 description 9
230000001575 pathological effect Effects 0.000 description 9
229920001223 polyethylene glycol Chemical class 0.000 description 9
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 9
239000013598 vector Substances 0.000 description 9
208000003174 Brain Neoplasms Diseases 0.000 description 8
102000004190 Enzymes Human genes 0.000 description 8
108090000790 Enzymes Proteins 0.000 description 8
239000002202 Polyethylene glycol Chemical class 0.000 description 8
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 8
238000009825 accumulation Methods 0.000 description 8
150000001408 amides Chemical class 0.000 description 8
210000001130 astrocyte Anatomy 0.000 description 8
208000019425 cirrhosis of liver Diseases 0.000 description 8
239000000032 diagnostic agent Substances 0.000 description 8
230000004927 fusion Effects 0.000 description 8
230000000144 pharmacologic effect Effects 0.000 description 8
150000003839 salts Chemical class 0.000 description 8
208000024891 symptom Diseases 0.000 description 8
229910052722 tritium Inorganic materials 0.000 description 8
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 7
241000699666 Mus <mouse, genus> Species 0.000 description 7
230000004071 biological effect Effects 0.000 description 7
229940039227 diagnostic agent Drugs 0.000 description 7
238000012377 drug delivery Methods 0.000 description 7
230000006870 function Effects 0.000 description 7
238000001727 in vivo Methods 0.000 description 7
208000015181 infectious disease Diseases 0.000 description 7
239000002105 nanoparticle Substances 0.000 description 7
230000001537 neural effect Effects 0.000 description 7
230000037361 pathway Effects 0.000 description 7
239000013612 plasmid Substances 0.000 description 7
230000003612 virological effect Effects 0.000 description 7
239000003643 water by type Substances 0.000 description 7
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
208000022873 Ocular disease Diseases 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
239000000969 carrier Substances 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
230000006378 damage Effects 0.000 description 6
229940000406 drug candidate Drugs 0.000 description 6
239000000700 radioactive tracer Substances 0.000 description 6
238000004007 reversed phase HPLC Methods 0.000 description 6
150000003384 small molecules Chemical class 0.000 description 6
239000007787 solid Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
150000003573 thiols Chemical class 0.000 description 6
231100000419 toxicity Toxicity 0.000 description 6
230000001988 toxicity Effects 0.000 description 6
ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 6
MQOAPJYYLUSVPA-UHFFFAOYSA-N 1-propanoylpyrrolidine-2,5-dione Chemical compound CCC(=O)N1C(=O)CCC1=O MQOAPJYYLUSVPA-UHFFFAOYSA-N 0.000 description 5
OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 description 5
XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
101710176384 Peptide 1 Proteins 0.000 description 5
101100510730 Rattus norvegicus Ldlr gene Proteins 0.000 description 5
208000006011 Stroke Diseases 0.000 description 5
238000003556 assay Methods 0.000 description 5
230000001580 bacterial effect Effects 0.000 description 5
210000004204 blood vessel Anatomy 0.000 description 5
210000004781 brain capillary Anatomy 0.000 description 5
210000001715 carotid artery Anatomy 0.000 description 5
238000003501 co-culture Methods 0.000 description 5
238000010511 deprotection reaction Methods 0.000 description 5
238000011161 development Methods 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
210000001163 endosome Anatomy 0.000 description 5
238000011065 in-situ storage Methods 0.000 description 5
238000001802 infusion Methods 0.000 description 5
210000003712 lysosome Anatomy 0.000 description 5
230000001868 lysosomic effect Effects 0.000 description 5
230000003071 parasitic effect Effects 0.000 description 5
238000003118 sandwich ELISA Methods 0.000 description 5
239000002356 single layer Substances 0.000 description 5
231100000331 toxic Toxicity 0.000 description 5
230000002588 toxic effect Effects 0.000 description 5
230000001052 transient effect Effects 0.000 description 5
108010078791 Carrier Proteins Proteins 0.000 description 4
108020004414 DNA Proteins 0.000 description 4
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
206010016654 Fibrosis Diseases 0.000 description 4
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
101100510727 Mus musculus Ldlr gene Proteins 0.000 description 4
208000027418 Wounds and injury Diseases 0.000 description 4
230000009471 action Effects 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000012412 chemical coupling Methods 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
230000007882 cirrhosis Effects 0.000 description 4
239000006274 endogenous ligand Substances 0.000 description 4
239000013604 expression vector Substances 0.000 description 4
239000012634 fragment Substances 0.000 description 4
208000014674 injury Diseases 0.000 description 4
238000007914 intraventricular administration Methods 0.000 description 4
150000002632 lipids Chemical class 0.000 description 4
239000002502 liposome Substances 0.000 description 4
201000007270 liver cancer Diseases 0.000 description 4
208000014018 liver neoplasm Diseases 0.000 description 4
DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 4
230000002132 lysosomal effect Effects 0.000 description 4
239000012528 membrane Substances 0.000 description 4
210000004379 membrane Anatomy 0.000 description 4
239000000178 monomer Substances 0.000 description 4
108010091867 peptide P Proteins 0.000 description 4
238000010647 peptide synthesis reaction Methods 0.000 description 4
230000035699 permeability Effects 0.000 description 4
239000000047 product Substances 0.000 description 4
238000000746 purification Methods 0.000 description 4
210000001525 retina Anatomy 0.000 description 4
230000002207 retinal effect Effects 0.000 description 4
210000003462 vein Anatomy 0.000 description 4
QGKMIGUHVLGJBR-UHFFFAOYSA-M (4z)-1-(3-methylbutyl)-4-[[1-(3-methylbutyl)quinolin-1-ium-4-yl]methylidene]quinoline;iodide Chemical compound [I-].C12=CC=CC=C2N(CCC(C)C)C=CC1=CC1=CC=[N+](CCC(C)C)C2=CC=CC=C12 QGKMIGUHVLGJBR-UHFFFAOYSA-M 0.000 description 3
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 3
102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 3
241000283690 Bos taurus Species 0.000 description 3
241000283707 Capra Species 0.000 description 3
230000005526 G1 to G0 transition Effects 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
241000711549 Hepacivirus C Species 0.000 description 3
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
239000004472 Lysine Substances 0.000 description 3
208000015439 Lysosomal storage disease Diseases 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
208000012902 Nervous system disease Diseases 0.000 description 3
208000025966 Neurological disease Diseases 0.000 description 3
208000018737 Parkinson disease Diseases 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
108010033576 Transferrin Receptors Proteins 0.000 description 3
102100026144 Transferrin receptor protein 1 Human genes 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
230000001919 adrenal effect Effects 0.000 description 3
150000001345 alkine derivatives Chemical class 0.000 description 3
WNNNWFKQCKFSDK-UHFFFAOYSA-N allylglycine Chemical compound OC(=O)C(N)CC=C WNNNWFKQCKFSDK-UHFFFAOYSA-N 0.000 description 3
229960002684 aminocaproic acid Drugs 0.000 description 3
230000001093 anti-cancer Effects 0.000 description 3
230000003140 astrocytic effect Effects 0.000 description 3
150000001540 azides Chemical class 0.000 description 3
230000008901 benefit Effects 0.000 description 3
229960002685 biotin Drugs 0.000 description 3
235000020958 biotin Nutrition 0.000 description 3
239000011616 biotin Substances 0.000 description 3
230000017531 blood circulation Effects 0.000 description 3
210000005098 blood-cerebrospinal fluid barrier Anatomy 0.000 description 3
235000012000 cholesterol Nutrition 0.000 description 3
230000008045 co-localization Effects 0.000 description 3
230000007423 decrease Effects 0.000 description 3
238000009792 diffusion process Methods 0.000 description 3
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 3
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
208000024386 fungal infectious disease Diseases 0.000 description 3
239000008103 glucose Substances 0.000 description 3
150000002333 glycines Chemical class 0.000 description 3
210000003494 hepatocyte Anatomy 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
102000043555 human LDLR Human genes 0.000 description 3
150000002431 hydrogen Chemical class 0.000 description 3
208000027866 inflammatory disease Diseases 0.000 description 3
230000010189 intracellular transport Effects 0.000 description 3
238000007913 intrathecal administration Methods 0.000 description 3
239000010410 layer Substances 0.000 description 3
230000000670 limiting effect Effects 0.000 description 3
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
230000036457 multidrug resistance Effects 0.000 description 3
230000035515 penetration Effects 0.000 description 3
239000000863 peptide conjugate Substances 0.000 description 3
238000005897 peptide coupling reaction Methods 0.000 description 3
150000003904 phospholipids Chemical class 0.000 description 3
239000000843 powder Substances 0.000 description 3
108010054624 red fluorescent protein Proteins 0.000 description 3
PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 3
XLXOKMFKGASILN-UHFFFAOYSA-N rhodamine red-X Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(=O)(=O)NCCCCCC(O)=O)C=C1S([O-])(=O)=O XLXOKMFKGASILN-UHFFFAOYSA-N 0.000 description 3
102000014452 scavenger receptors Human genes 0.000 description 3
108010078070 scavenger receptors Proteins 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
230000000946 synaptic effect Effects 0.000 description 3
238000002560 therapeutic procedure Methods 0.000 description 3
HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 3
FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 2
XCIRMLHOFVDUDP-BYPYZUCNSA-N (2r)-3-acetylsulfanyl-2-aminopropanoic acid Chemical compound CC(=O)SC[C@H](N)C(O)=O XCIRMLHOFVDUDP-BYPYZUCNSA-N 0.000 description 2
108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
DGYHPLMPMRKMPD-UHFFFAOYSA-N 2-azaniumylpent-4-ynoate Chemical compound OC(=O)C(N)CC#C DGYHPLMPMRKMPD-UHFFFAOYSA-N 0.000 description 2
XCIRMLHOFVDUDP-UHFFFAOYSA-N 3-acetylsulfanyl-2-aminopropanoic acid Chemical compound CC(=O)SCC(N)C(O)=O XCIRMLHOFVDUDP-UHFFFAOYSA-N 0.000 description 2
DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 2
208000036443 AIPL1-related retinopathy Diseases 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
208000024827 Alzheimer disease Diseases 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
206010009944 Colon cancer Diseases 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
238000002965 ELISA Methods 0.000 description 2
238000012286 ELISA Assay Methods 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
239000007821 HATU Substances 0.000 description 2
108010010234 HDL Lipoproteins Proteins 0.000 description 2
102400001369 Heparin-binding EGF-like growth factor Human genes 0.000 description 2
101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 2
206010019799 Hepatitis viral Diseases 0.000 description 2
101000871708 Homo sapiens Proheparin-binding EGF-like growth factor Proteins 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
206010020961 Hypocholesterolaemia Diseases 0.000 description 2
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 2
102000003746 Insulin Receptor Human genes 0.000 description 2
108010001127 Insulin Receptor Proteins 0.000 description 2
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
102100038204 Large neutral amino acids transporter small subunit 1 Human genes 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
YPIGGYHFMKJNKV-UHFFFAOYSA-N N-ethylglycine Chemical compound CC[NH2+]CC([O-])=O YPIGGYHFMKJNKV-UHFFFAOYSA-N 0.000 description 2
108010065338 N-ethylglycine Proteins 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
102100033762 Proheparin-binding EGF-like growth factor Human genes 0.000 description 2
102000004079 Prolyl Hydroxylases Human genes 0.000 description 2
108010043005 Prolyl Hydroxylases Proteins 0.000 description 2
102000006382 Ribonucleases Human genes 0.000 description 2
108010083644 Ribonucleases Proteins 0.000 description 2
108091006232 SLC7A5 Proteins 0.000 description 2
229910006069 SO3H Inorganic materials 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
102000004584 Somatomedin Receptors Human genes 0.000 description 2
108010017622 Somatomedin Receptors Proteins 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
229920004890 Triton X-100 Polymers 0.000 description 2
108010062497 VLDL Lipoproteins Proteins 0.000 description 2
208000036142 Viral infection Diseases 0.000 description 2
241000700605 Viruses Species 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
230000009056 active transport Effects 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
238000013459 approach Methods 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
210000005100 blood-tumour barrier Anatomy 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000007853 buffer solution Substances 0.000 description 2
OWIUPIRUAQMTTK-UHFFFAOYSA-N carbazic acid Chemical compound NNC(O)=O OWIUPIRUAQMTTK-UHFFFAOYSA-N 0.000 description 2
125000002091 cationic group Chemical group 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
239000013592 cell lysate Substances 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
210000003710 cerebral cortex Anatomy 0.000 description 2
210000001175 cerebrospinal fluid Anatomy 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
230000004087 circulation Effects 0.000 description 2
201000006754 cone-rod dystrophy Diseases 0.000 description 2
238000010226 confocal imaging Methods 0.000 description 2
239000000470 constituent Substances 0.000 description 2
230000001086 cytosolic effect Effects 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000013461 design Methods 0.000 description 2
238000001514 detection method Methods 0.000 description 2
229960004679 doxorubicin Drugs 0.000 description 2
230000035622 drinking Effects 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000000132 electrospray ionisation Methods 0.000 description 2
210000003038 endothelium Anatomy 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
238000002641 enzyme replacement therapy Methods 0.000 description 2
206010015037 epilepsy Diseases 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
238000013213 extrapolation Methods 0.000 description 2
208000030533 eye disease Diseases 0.000 description 2
238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
239000012458 free base Substances 0.000 description 2
102000037865 fusion proteins Human genes 0.000 description 2
108020001507 fusion proteins Proteins 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
208000005017 glioblastoma Diseases 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
150000002433 hydrophilic molecules Chemical class 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
238000003365 immunocytochemistry Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000003993 interaction Effects 0.000 description 2
230000000968 intestinal effect Effects 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
239000008101 lactose Substances 0.000 description 2
230000003902 lesion Effects 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 2
235000018977 lysine Nutrition 0.000 description 2
229920002521 macromolecule Polymers 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
238000001000 micrograph Methods 0.000 description 2
238000001823 molecular biology technique Methods 0.000 description 2
239000013642 negative control Substances 0.000 description 2
210000000944 nerve tissue Anatomy 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
150000002894 organic compounds Chemical class 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000008188 pellet Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
230000003285 pharmacodynamic effect Effects 0.000 description 2
XRBCRPZXSCBRTK-UHFFFAOYSA-N phosphonous acid Chemical compound OPO XRBCRPZXSCBRTK-UHFFFAOYSA-N 0.000 description 2
HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 2
230000002265 prevention Effects 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 2
230000017854 proteolysis Effects 0.000 description 2
230000002285 radioactive effect Effects 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000011084 recovery Methods 0.000 description 2
230000009467 reduction Effects 0.000 description 2
229940055619 selenocysteine Drugs 0.000 description 2
ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 2
235000016491 selenocysteine Nutrition 0.000 description 2
239000008247 solid mixture Substances 0.000 description 2
239000007790 solid phase Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
238000001179 sorption measurement Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
239000000454 talc Substances 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
238000001890 transfection Methods 0.000 description 2
238000012546 transfer Methods 0.000 description 2
210000003956 transport vesicle Anatomy 0.000 description 2
238000005533 tritiation Methods 0.000 description 2
210000004881 tumor cell Anatomy 0.000 description 2
201000001862 viral hepatitis Diseases 0.000 description 2
QZRUMKUMFJJARD-AAJWHBHYSA-N (+/-)-butaclamol hydrochloride Chemical compound Cl.C12=CC=CC=C2CCC2=CC=CC3=C2[C@H]1CN1CC[C@](C(C)(C)C)(O)C[C@H]13 QZRUMKUMFJJARD-AAJWHBHYSA-N 0.000 description 1
BJBUEDPLEOHJGE-UHFFFAOYSA-N (2R,3S)-3-Hydroxy-2-pyrolidinecarboxylic acid Natural products OC1CCNC1C(O)=O BJBUEDPLEOHJGE-UHFFFAOYSA-N 0.000 description 1
UMRUUWFGLGNQLI-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UMRUUWFGLGNQLI-QFIPXVFZSA-N 0.000 description 1
JBDOTWVUXVXVDR-YCXLAJEKSA-N (2s)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid Chemical compound OC(=O)[C@H]1NCC2CC12 JBDOTWVUXVXVDR-YCXLAJEKSA-N 0.000 description 1
CNPSFBUUYIVHAP-AKGZTFGVSA-N (2s)-3-methylpyrrolidine-2-carboxylic acid Chemical compound CC1CCN[C@@H]1C(O)=O CNPSFBUUYIVHAP-AKGZTFGVSA-N 0.000 description 1
SHINASQYHDCLEU-BKLSDQPFSA-N (2s)-4-aminopyrrolidine-2-carboxylic acid Chemical compound NC1CN[C@H](C(O)=O)C1 SHINASQYHDCLEU-BKLSDQPFSA-N 0.000 description 1
GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 description 1
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
WOXWUZCRWJWTRT-UHFFFAOYSA-N 1-amino-1-cyclohexanecarboxylic acid Chemical compound OC(=O)C1(N)CCCCC1 WOXWUZCRWJWTRT-UHFFFAOYSA-N 0.000 description 1
JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
RIJNIVWHYSNSLQ-UHFFFAOYSA-N 2-(2,3-dihydro-1h-inden-2-ylazaniumyl)acetate Chemical compound C1=CC=C2CC(NCC(=O)O)CC2=C1 RIJNIVWHYSNSLQ-UHFFFAOYSA-N 0.000 description 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical class NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
JINGUCXQUOKWKH-UHFFFAOYSA-N 2-aminodecanoic acid Chemical compound CCCCCCCCC(N)C(O)=O JINGUCXQUOKWKH-UHFFFAOYSA-N 0.000 description 1
QGJGBYXRJVIYGA-UHFFFAOYSA-N 2-azaniumyl-2-(4-chlorophenyl)acetate Chemical compound OC(=O)C(N)C1=CC=C(Cl)C=C1 QGJGBYXRJVIYGA-UHFFFAOYSA-N 0.000 description 1
WAMWSIDTKSNDCU-UHFFFAOYSA-N 2-azaniumyl-2-cyclohexylacetate Chemical compound OC(=O)C(N)C1CCCCC1 WAMWSIDTKSNDCU-UHFFFAOYSA-N 0.000 description 1
XBPKRVHTESHFAA-UHFFFAOYSA-N 2-azaniumyl-2-cyclopentylacetate Chemical compound OC(=O)C(N)C1CCCC1 XBPKRVHTESHFAA-UHFFFAOYSA-N 0.000 description 1
LPBSHGLDBQBSPI-UHFFFAOYSA-N 2-azaniumyl-4,4-dimethylpentanoate Chemical compound CC(C)(C)CC(N)C(O)=O LPBSHGLDBQBSPI-UHFFFAOYSA-N 0.000 description 1
BMLMGCPTLHPWPY-UHFFFAOYSA-N 2-oxo-1,3-thiazolidine-4-carboxylic acid Chemical compound OC(=O)C1CSC(=O)N1 BMLMGCPTLHPWPY-UHFFFAOYSA-N 0.000 description 1
ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
FZTIWOBQQYPTCJ-UHFFFAOYSA-N 4-[4-(4-carboxyphenyl)phenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(O)=O)C=C1 FZTIWOBQQYPTCJ-UHFFFAOYSA-N 0.000 description 1
WFJIVOKAWHGMBH-UHFFFAOYSA-N 4-hexylbenzene-1,3-diol Chemical compound CCCCCCC1=CC=C(O)C=C1O WFJIVOKAWHGMBH-UHFFFAOYSA-N 0.000 description 1
HFXAFXVXPMUQCQ-BYPYZUCNSA-N 4-oxo-L-proline Chemical compound OC(=O)[C@@H]1CC(=O)CN1 HFXAFXVXPMUQCQ-BYPYZUCNSA-N 0.000 description 1
UAISREBYDOFHJY-UHFFFAOYSA-N 4-oxopiperidin-1-ium-2-carboxylate Chemical compound OC(=O)C1CC(=O)CCN1 UAISREBYDOFHJY-UHFFFAOYSA-N 0.000 description 1
YIUIVFFUEVPRIU-UHFFFAOYSA-N 8-chlorotheophylline Chemical compound O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21 YIUIVFFUEVPRIU-UHFFFAOYSA-N 0.000 description 1
208000030507 AIDS Diseases 0.000 description 1
235000001291 Aechmea magdalenae Nutrition 0.000 description 1
244000179819 Aechmea magdalenae Species 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
102100029470 Apolipoprotein E Human genes 0.000 description 1
101710095339 Apolipoprotein E Proteins 0.000 description 1
108010071619 Apolipoproteins Proteins 0.000 description 1
102000007592 Apolipoproteins Human genes 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
206010003805 Autism Diseases 0.000 description 1
208000020706 Autistic disease Diseases 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
102000004506 Blood Proteins Human genes 0.000 description 1
108010017384 Blood Proteins Proteins 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
102400000967 Bradykinin Human genes 0.000 description 1
101800004538 Bradykinin Proteins 0.000 description 1
208000014644 Brain disease Diseases 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
102000053642 Catalytic RNA Human genes 0.000 description 1
108090000994 Catalytic RNA Proteins 0.000 description 1
102000004225 Cathepsin B Human genes 0.000 description 1
108090000712 Cathepsin B Proteins 0.000 description 1
206010008190 Cerebrovascular accident Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
102000004266 Collagen Type IV Human genes 0.000 description 1
108010042086 Collagen Type IV Proteins 0.000 description 1
208000001333 Colorectal Neoplasms Diseases 0.000 description 1
208000032170 Congenital Abnormalities Diseases 0.000 description 1
208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
102000053602 DNA Human genes 0.000 description 1
UQBOJOOOTLPNST-UHFFFAOYSA-N Dehydroalanine Chemical compound NC(=C)C(O)=O UQBOJOOOTLPNST-UHFFFAOYSA-N 0.000 description 1
206010012689 Diabetic retinopathy Diseases 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
241000283074 Equus asinus Species 0.000 description 1
102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
102100037362 Fibronectin Human genes 0.000 description 1
108010067306 Fibronectins Proteins 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
229930182566 Gentamicin Natural products 0.000 description 1
QMXOFBXZEKTJIK-UHFFFAOYSA-N Glycinol Natural products C1=C(O)C=C2OCC3(O)C4=CC=C(O)C=C4OC3C2=C1 QMXOFBXZEKTJIK-UHFFFAOYSA-N 0.000 description 1
QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
241000711557 Hepacivirus Species 0.000 description 1
241000700721 Hepatitis B virus Species 0.000 description 1
241000282412 Homo Species 0.000 description 1
101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
DZLNHFMRPBPULJ-VKHMYHEASA-N L-thioproline Chemical compound OC(=O)[C@@H]1CSCN1 DZLNHFMRPBPULJ-VKHMYHEASA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
102100034238 Linker for activation of T-cells family member 2 Human genes 0.000 description 1
101710172064 Low-density lipoprotein receptor-related protein Proteins 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
NVGBPTNZLWRQSY-UWVGGRQHSA-N Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN NVGBPTNZLWRQSY-UWVGGRQHSA-N 0.000 description 1
PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
241000466402 Molema Species 0.000 description 1
241001092142 Molina Species 0.000 description 1
241001529936 Murinae Species 0.000 description 1
208000031888 Mycoses Diseases 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
108090000189 Neuropeptides Proteins 0.000 description 1
102000003797 Neuropeptides Human genes 0.000 description 1
102000012106 Neutral Amino Acid Transport Systems Human genes 0.000 description 1
108010036505 Neutral Amino Acid Transport Systems Proteins 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
108091028043 Nucleic acid sequence Proteins 0.000 description 1
239000004677 Nylon Substances 0.000 description 1
238000011795 OF1 mouse Methods 0.000 description 1
108091034117 Oligonucleotide Proteins 0.000 description 1
108010093625 Opioid Peptides Proteins 0.000 description 1
102000001490 Opioid Peptides Human genes 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
206010061535 Ovarian neoplasm Diseases 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
206010061902 Pancreatic neoplasm Diseases 0.000 description 1
102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
208000030852 Parasitic disease Diseases 0.000 description 1
101710149632 Pectinesterase A Proteins 0.000 description 1
KRHNXNZBLHHEIU-UHFFFAOYSA-N Pegaline Natural products OC1CCNC(C(O)=O)C1 KRHNXNZBLHHEIU-UHFFFAOYSA-N 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108010004729 Phycoerythrin Proteins 0.000 description 1
208000012654 Primary biliary cholangitis Diseases 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
239000004365 Protease Substances 0.000 description 1
229940096437 Protein S Drugs 0.000 description 1
108030003943 Protein-disulfide reductases Proteins 0.000 description 1
208000007660 Residual Neoplasm Diseases 0.000 description 1
206010038848 Retinal detachment Diseases 0.000 description 1
208000007014 Retinitis pigmentosa Diseases 0.000 description 1
201000000582 Retinoblastoma Diseases 0.000 description 1
206010038926 Retinopathy hypertensive Diseases 0.000 description 1
IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
108091005487 SCARB1 Proteins 0.000 description 1
108091006238 SLC7A8 Proteins 0.000 description 1
WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
102100037118 Scavenger receptor class B member 1 Human genes 0.000 description 1
108020004459 Small interfering RNA Proteins 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
229920002253 Tannate Polymers 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102000004338 Transferrin Human genes 0.000 description 1
108090000901 Transferrin Proteins 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 1
108070000030 Viral receptors Proteins 0.000 description 1
102100035140 Vitronectin Human genes 0.000 description 1
108010031318 Vitronectin Proteins 0.000 description 1
239000003875 Wang resin Substances 0.000 description 1
HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 1
NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical group C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
239000002250 absorbent Substances 0.000 description 1
230000002745 absorbent Effects 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
229960004150 aciclovir Drugs 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
231100000354 acute hepatitis Toxicity 0.000 description 1
229960001997 adefovir Drugs 0.000 description 1
WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 1
201000005188 adrenal gland cancer Diseases 0.000 description 1
208000024447 adrenal gland neoplasm Diseases 0.000 description 1
238000012382 advanced drug delivery Methods 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
108010004469 allophycocyanin Proteins 0.000 description 1
AFVLVVWMAFSXCK-VMPITWQZSA-N alpha-cyano-4-hydroxycinnamic acid Chemical compound OC(=O)C(\C#N)=C\C1=CC=C(O)C=C1 AFVLVVWMAFSXCK-VMPITWQZSA-N 0.000 description 1
CJCSPKMFHVPWAR-JTQLQIEISA-N alpha-methyl-L-dopa Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 CJCSPKMFHVPWAR-JTQLQIEISA-N 0.000 description 1
ZGUNAGUHMKGQNY-UHFFFAOYSA-N alpha-phenylglycine Chemical compound OC(=O)C(N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-UHFFFAOYSA-N 0.000 description 1
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
PZZYQPZGQPZBDN-UHFFFAOYSA-N aluminium silicate Chemical compound O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 description 1
229910000323 aluminium silicate Inorganic materials 0.000 description 1
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
239000012491 analyte Substances 0.000 description 1
230000033115 angiogenesis Effects 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000003510 anti-fibrotic effect Effects 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
229940124599 anti-inflammatory drug Drugs 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
230000000840 anti-viral effect Effects 0.000 description 1
239000000427 antigen Substances 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
229940041181 antineoplastic drug Drugs 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
208000008784 apnea Diseases 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
208000037849 arterial hypertension Diseases 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
OISFUZRUIGGTSD-LJTMIZJLSA-N azane;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound N.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO OISFUZRUIGGTSD-LJTMIZJLSA-N 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
239000002585 base Substances 0.000 description 1
210000002469 basement membrane Anatomy 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
ADSALMJPJUKESW-UHFFFAOYSA-N beta-Homoproline Chemical compound OC(=O)CC1CCCN1 ADSALMJPJUKESW-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
108091008324 binding proteins Proteins 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
230000007698 birth defect Effects 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
208000005881 bovine spongiform encephalopathy Diseases 0.000 description 1
QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
210000004958 brain cell Anatomy 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
230000004611 cancer cell death Effects 0.000 description 1
210000001043 capillary endothelial cell Anatomy 0.000 description 1
150000004657 carbamic acid derivatives Chemical class 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
201000011529 cardiovascular cancer Diseases 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
238000010382 chemical cross-linking Methods 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
BJBUEDPLEOHJGE-IUYQGCFVSA-N cis-3-hydroxy-D-proline zwitterion Chemical compound O[C@H]1CCN[C@H]1C(O)=O BJBUEDPLEOHJGE-IUYQGCFVSA-N 0.000 description 1
229940090805 clavulanate Drugs 0.000 description 1
HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
238000004624 confocal microscopy Methods 0.000 description 1
230000001268 conjugating effect Effects 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
230000001054 cortical effect Effects 0.000 description 1
239000012228 culture supernatant Substances 0.000 description 1
238000005520 cutting process Methods 0.000 description 1
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
239000002254 cytotoxic agent Substances 0.000 description 1
231100000599 cytotoxic agent Toxicity 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000001934 delay Effects 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000010586 diagram Methods 0.000 description 1
ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
230000003467 diminishing effect Effects 0.000 description 1
239000001177 diphosphate Substances 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
150000002019 disulfides Chemical class 0.000 description 1
POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
XAMAATKKOCZRPP-UHFFFAOYSA-N dodecyl hydrogen sulfate;propanoic acid Chemical compound CCC(O)=O.CCCCCCCCCCCCOS(O)(=O)=O XAMAATKKOCZRPP-UHFFFAOYSA-N 0.000 description 1
239000000890 drug combination Substances 0.000 description 1
238000009509 drug development Methods 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
239000000975 dye Substances 0.000 description 1
229940009662 edetate Drugs 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
229950005627 embonate Drugs 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
206010014599 encephalitis Diseases 0.000 description 1
230000008290 endocytic mechanism Effects 0.000 description 1
230000003511 endothelial effect Effects 0.000 description 1
210000003989 endothelium vascular Anatomy 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
231100000318 excitotoxic Toxicity 0.000 description 1
230000003492 excitotoxic effect Effects 0.000 description 1
230000029142 excretion Effects 0.000 description 1
238000013265 extended release Methods 0.000 description 1
210000003722 extracellular fluid Anatomy 0.000 description 1
210000001723 extracellular space Anatomy 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
238000000684 flow cytometry Methods 0.000 description 1
239000007850 fluorescent dye Substances 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
229960002870 gabapentin Drugs 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
229960002518 gentamicin Drugs 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 description 1
239000008187 granular material Substances 0.000 description 1
210000004884 grey matter Anatomy 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
210000003128 head Anatomy 0.000 description 1
208000006454 hepatitis Diseases 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
229960003258 hexylresorcinol Drugs 0.000 description 1
230000013632 homeostatic process Effects 0.000 description 1
150000002429 hydrazines Chemical class 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
229960002591 hydroxyproline Drugs 0.000 description 1
201000001948 hypertensive retinopathy Diseases 0.000 description 1
239000012729 immediate-release (IR) formulation Substances 0.000 description 1
239000002955 immunomodulating agent Substances 0.000 description 1
230000002584 immunomodulator Effects 0.000 description 1
229940121354 immunomodulator Drugs 0.000 description 1
238000012744 immunostaining Methods 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000010874 in vitro model Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
229940042040 innovative drug Drugs 0.000 description 1
238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
230000009545 invasion Effects 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
210000003292 kidney cell Anatomy 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-M lactobionate Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-M 0.000 description 1
229940070765 laurate Drugs 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
150000002617 leukotrienes Chemical class 0.000 description 1
230000029226 lipidation Effects 0.000 description 1
208000019423 liver disease Diseases 0.000 description 1
230000007774 longterm Effects 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
210000004324 lymphatic system Anatomy 0.000 description 1
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
150000002669 lysines Chemical class 0.000 description 1
108010054155 lysyllysine Proteins 0.000 description 1
208000002780 macular degeneration Diseases 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
235000001055 magnesium Nutrition 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
239000000391 magnesium silicate Substances 0.000 description 1
229910052919 magnesium silicate Inorganic materials 0.000 description 1
235000019792 magnesium silicate Nutrition 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000003550 marker Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
229960001924 melphalan Drugs 0.000 description 1
210000002418 meninge Anatomy 0.000 description 1
229960003151 mercaptamine Drugs 0.000 description 1
DWPCPZJAHOETAG-UHFFFAOYSA-N meso-lanthionine Natural products OC(=O)C(N)CSCC(N)C(O)=O DWPCPZJAHOETAG-UHFFFAOYSA-N 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
108091070501 miRNA Proteins 0.000 description 1
239000000693 micelle Substances 0.000 description 1
239000002679 microRNA Substances 0.000 description 1
210000000274 microglia Anatomy 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
210000005099 mouse brain capillary cell Anatomy 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
230000023105 myelination Effects 0.000 description 1
CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 1
239000002088 nanocapsule Substances 0.000 description 1
239000002077 nanosphere Substances 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
239000006225 natural substrate Substances 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
230000000626 neurodegenerative effect Effects 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000002981 neuropathic effect Effects 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
229920001778 nylon Polymers 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
239000003399 opiate peptide Substances 0.000 description 1
229940100688 oral solution Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
201000002528 pancreatic cancer Diseases 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
229940014662 pantothenate Drugs 0.000 description 1
239000011713 pantothenic acid Substances 0.000 description 1
235000019161 pantothenic acid Nutrition 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000009057 passive transport Effects 0.000 description 1
244000052769 pathogen Species 0.000 description 1
210000003668 pericyte Anatomy 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
229960004838 phosphoric acid Drugs 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
229940075930 picrate Drugs 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
239000006187 pill Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
239000012704 polymeric precursor Substances 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229950008882 polysorbate Drugs 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229940068968 polysorbate 80 Drugs 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000011148 porous material Substances 0.000 description 1
231100000683 possible toxicity Toxicity 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
238000011002 quantification Methods 0.000 description 1
238000000163 radioactive labelling Methods 0.000 description 1
238000011552 rat model Methods 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
230000010837 receptor-mediated endocytosis Effects 0.000 description 1
230000003134 recirculating effect Effects 0.000 description 1
238000004064 recycling Methods 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004264 retinal detachment Effects 0.000 description 1
210000003583 retinal pigment epithelium Anatomy 0.000 description 1
210000001210 retinal vessel Anatomy 0.000 description 1
238000012552 review Methods 0.000 description 1
229960000329 ribavirin Drugs 0.000 description 1
HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
108091092562 ribozyme Proteins 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
229920002477 rna polymer Polymers 0.000 description 1
235000002020 sage Nutrition 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
239000002924 silencing RNA Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
208000020431 spinal cord injury Diseases 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
229940071103 sulfosalicylate Drugs 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
238000011191 terminal modification Methods 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229940126585 therapeutic drug Drugs 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
210000001578 tight junction Anatomy 0.000 description 1
239000003440 toxic substance Substances 0.000 description 1
238000002627 tracheal intubation Methods 0.000 description 1
230000003723 transcellular diffusion Effects 0.000 description 1
230000031998 transcytosis Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
230000007723 transport mechanism Effects 0.000 description 1
239000013638 trimer Substances 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
238000000825 ultraviolet detection Methods 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
238000010200 validation analysis Methods 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
230000002227 vasoactive effect Effects 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
239000002676 xenobiotic agent Substances 0.000 description 1
AFVLVVWMAFSXCK-UHFFFAOYSA-N α-cyano-4-hydroxycinnamic acid Chemical compound OC(=O)C(C#N)=CC1=CC=C(O)C=C1 AFVLVVWMAFSXCK-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Medicinal Chemistry (AREA)
Health & Medical Sciences (AREA)
Biochemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Preparation (AREA)
Peptides Or Proteins (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CN201380065295.4A 2012-10-19 2013-10-18 用于药物递送的组合物和方法 Active CN105050612B (zh)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US13/655,954 US8877716B2 (en)	2010-04-21	2012-10-19	Peptide derivatives, preparation and uses thereof
US13/655,954		2012-10-19
PCT/EP2013/071898 WO2014060601A1 (en)	2012-10-19	2013-10-18	Compositions and methods for drug delivery

Publications (2)

Publication Number	Publication Date
CN105050612A CN105050612A (zh)	2015-11-11
CN105050612B true CN105050612B (zh)	2018-04-20

Family

ID=50488949

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CN201380065295.4A Active CN105050612B (zh)	2012-10-19	2013-10-18	用于药物递送的组合物和方法

Country Status (5)

Country	Link
EP (1)	EP2908837B1 (ja)
JP (1)	JP6426100B2 (ja)
CN (1)	CN105050612B (ja)
PL (1)	PL2908837T3 (ja)
WO (1)	WO2014060601A1 (ja)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN110536705A (zh) *	2017-01-30	2019-12-03	维克塔-霍洛斯公司	用于癌症成像和放疗的组合物和方法
CN109384850A (zh) *	2017-08-11	2019-02-26	复旦大学	全过程靶向多肽及其在构建肿瘤靶向诊治递药***中的应用
WO2022156531A1 (zh) *	2021-01-19	2022-07-28	中国人民解放军军事科学院军事医学研究院	一种能够透过生物屏障的动力蛋白结合肽及其应用
WO2023198204A1 (zh) *	2022-04-14	2023-10-19	苏州瑞博生物技术股份有限公司	缀合物、含有该缀合物的药物组合物及制备方法和用途
CN118005762A (zh) *	2023-08-29	2024-05-10	北京大学	靶向清道夫受体的多肽配体、非共价双靶向分子及其制药用途

Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2796174A1 (en) *	2010-04-21	2011-10-27	Centre National De La Recherche Scientifique	Peptide derivatives, preparation thereof and uses thereof

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2002511844A (ja) *	1997-04-11	2002-04-16	ロシュダイアグノスティックスゲーエムベーハー	ウロキナーゼレセプターの阻害
KR101111477B1 (ko) *	2002-12-03	2012-02-23	블랜체트 록펠러 뉴로사이언시즈 인스티튜트	치료제와 연결된 콜레스테롤을 포함하는 접합체
FR2937322B1 (fr)	2008-10-22	2013-02-22	Vect Horus	Derives peptidiques et leur utilisation comme vecteurs de molecules sous forme de conjugues
WO2010108048A2 (en) *	2009-03-18	2010-09-23	Armagen Technologies, Inc.	Compositions and methods for blood-brain barrier delivery of igg-decoy receptor fusion proteins
EP2343081A1 (en) *	2009-12-31	2011-07-13	Rijksuniversiteit Groningen	Interferon analogs
WO2012133349A1 (ja) *	2011-03-25	2012-10-04	株式会社カネカ	アフィニティー分離マトリックス用タンパク質

2013
- 2013-10-18 WO PCT/EP2013/071898 patent/WO2014060601A1/en active Application Filing
- 2013-10-18 CN CN201380065295.4A patent/CN105050612B/zh active Active
- 2013-10-18 PL PL13783290T patent/PL2908837T3/pl unknown
- 2013-10-18 EP EP13783290.3A patent/EP2908837B1/en active Active
- 2013-10-18 JP JP2015537280A patent/JP6426100B2/ja active Active

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2796174A1 (en) *	2010-04-21	2011-10-27	Centre National De La Recherche Scientifique	Peptide derivatives, preparation thereof and uses thereof

Also Published As

Publication number	Publication date
EP2908837B1 (en)	2019-02-13
JP2015536315A (ja)	2015-12-21
WO2014060601A1 (en)	2014-04-24
EP2908837A1 (en)	2015-08-26
PL2908837T3 (pl)	2019-08-30
JP6426100B2 (ja)	2018-11-21
CN105050612A (zh)	2015-11-11

Legal Events

Date	Code	Title
2015-11-11	C06	Publication
2015-11-11	PB01	Publication
2015-12-09	C10	Entry into substantive examination
2015-12-09	SE01	Entry into force of request for substantive examination
2018-04-20	GR01	Patent grant
2018-04-20	GR01	Patent grant

Publication	Publication Date	Title
DK2908837T3 (en)	2019-04-23	PHARMACEUTICAL DELIVERY COMPOSITIONS
JP6232396B2 (ja)	2017-11-15	ペプチド誘導体、およびコンジュゲートの形態での分子用ベクターとしてのそれらの使用
JP5264502B2 (ja)	2013-08-14	細胞透過性ペプチドとして使用できるペプチド
CN105050612B (zh)	2018-04-20	用于药物递送的组合物和方法
CN113597318A (zh)	2021-11-02	治疗性纳米缀合物及其用途